CD98(SLC3A2) has a heteromeric structure, consisting of a heavy subunit linked to a light subunit via disulfide bridges, CD98, originally identified as the 4F2 antigen, is a cell surface molecule, which is highly expressed in activated T cells, proliferating endothelial cells, and proliferating fibroblasts. The heavy subunit is a type II transmembrane glycoprotein associated with one of seven different light chains. The latter ones provide amino acid transport activity of CD98, while the heavy chain (CD98hc) is thought to mediate adhesion induced signal transduction via integrins [1]. Disruption of the CD98hc gene led to embryonic lethality between day E 3.5 and E 9.5 [2, 3]. Deletion of CD98hc in embryonic stem cells blocked their ability to form teratocarcinomas in vivo transplants in mice [2], while inhibition of CD98hc in vitro led to reduced cell growth and apoptosis in embryonic stem cells [4]. Over-expression of CD98hc in murine fibroblasts resulted in anchorage-independent growth [5]. In this PhD - thesis CD98hc was identified as a novel diagnostic marker for malignant renal cell cancer, among them clear cell renal cell cancer, papillary as well as chromphobe renal cell cancer. Thereby, level of CD98hc expression correlated with grade of differentiation, whereby the more malignant grade3/ grade4 ccRCC or type II pRCC revealed significant higher CD98hc expression in semi-quantitative analyses. Furthermore, by a combination of loss and gain of function approaches a hitherto undescribed functional role of CD98hc in tumor cell behavior such as tumor cell proliferation, cell survival upon detachment, cell migration or spreading was revealed. In conclusion these data indicated that CD98hc is not only a novel biomarker in RCC, but might also represent a pathological diagnostic target in cancer.